By Diagnostics World Staff
November 17, 2017 | The Association for Molecular Pathology (AMP) published 17 consensus recommendations to help clinical laboratory professionals achieve high-quality sequencing results and deliver better patient care. The report, “Standards and Guidelines for Validating Next Generation Sequencing Bioinformatics Pipelines: A Joint Recommendation of the Association for Molecular Pathology and College of American Pathologists,” was released yesterday online ahead of publication in The Journal of Molecular Diagnostics.
“While the recent widespread adoption of next-generation sequencing (NGS) methodologies [has] transformed our ability to detect somatic and germline variants, the constant technology evolution and absence of professional guidelines have contributed to variability in clinical laboratory practice,” said Somak Roy, MD, Assistant Professor of Pathology at University of Pittsburgh Medical Center, Working Group Chair and AMP Member. “To help solve this unmet need, AMP convened and led a multidisciplinary subject matter expert working group with representation from the College of American Pathologists (CAP), and the American Medical Informatics Association (AMIA) to summarize current knowledge, expose challenges and provide guidance on how to develop, implement and validate high-quality bioinformatics pipelines to ensure better overall patient care.”
The new bioinformatics report (DOI: http://dx.doi.org/10.1016/j.jmoldx.2017.11.003) emphasizes the critical role of the properly-trained molecular laboratory professional and recommends practical advice for laboratories regarding bioinformatics pipeline design, development, validation, and operation. Among the 17 guidelines:
- Clinical laboratories offering NGS-based testing should perform their own validation of the bioinformatics pipeline
- The bioinformatics pipeline is part of the test procedure, and its components and processes must be documented according to laboratory accreditation standards and regulations
- The identity of the sample must be preserved throughout each step of the NGS bioinformatics pipeline with a minimum of four unique identifiers including a unique location identifier within the content of each data file read and/or generated by the pipeline
- Laboratories must include specific measures to ensure that each data file generated in the bioinformatics pipeline maintains its integrity and provides alerts for or prevents the use of data files which have been altered in an unauthorized or unintended manner
- In silico validation can be used to supplement the validation of the bioinformatics pipeline but shall not be used in lieu of end-to-end validation of the bioinformatics pipelines using human samples
- Clinical laboratories must ensure the accuracy of software-generated HGVS variant nomenclature and annotations and have an alert in place to indicate when the software-generated nomenclature and annotations need to be manually reviewed and/or corrected, and documentation of any corrections must be maintained
The report is the final one in a series of guidelines AMP has recently published including. Previously AMP has offered guidelines on interpreting oncology sequence variants, and next-generation sequencing-based oncology panel validation.
“AMP members are among the early adopters and users of NGS technology in a clinical setting and these best practice consensus standards and guidelines are based on our collective knowledge and expertise,” said Alexis B. Carter, MD, Physician Informaticist at Children's Healthcare of Atlanta, Working Group Member, 2017 AMP Informatics Subdivision Chair, and AMP Board Member. “With this series of three guidelines addressing the complete NGS workflow, AMP has now provided the entire cancer genomics community with the appropriate tools and guidance to better incorporate the latest technological innovations in molecular pathology.”
All three reports are based on evidence from a review of published literature, empirical data, current laboratory practice surveys, feedback from multiple public meetings, and expert professional experiences. Since these recommendations represent current best practice in a rapidly developing field, AMP anticipates a need for ongoing updates.